The human T cell leukemia virus, HTLV-1 is the etiologic agent of adult T cell leukemia lymphoma. This virus is endemic to several areas of the world and the disease caused by this virus, although rare, is an extremely aggressive neoplasm with a high fatality rate. These cells appear to be able to overcome the normal dependence of T cells on the growth factor, interleukin 2 (IL2), and grow autonomously in its absence. The virus encodes two proteins which appear to influence cellular as well as viral gene expression. The tax protein is known to be a transactivator of transcription and to influence cellular as well as viral promoter activity. The second product, the rex-protein, has also recently been shown to influence cellular gene expression. Two of the cellular genes known to be upregulated in their expression by tax and rex are those for IL2 and its receptor. The goal of this proposal is to understand how the rex gene product influences IL2 gene expression and what cellular factors might be involved in the upregulation. Promoter deletion and mutation analysis will be used to identify the sequences involved in rex mediated transactivation of IL2 promoter activity. Cell lines which can be induced for expression of tax and/or rex will be used for the analysis of the rex affect on endogenous IL2 gene expression. Gel migration retardation assays will be used to verify the identity of transcription enhancing factors whose activities are influenced by the presence of the tax and rex proteins. Finally, experiments have been designed to determine the mechanism of action used by the rex protein to up-regulate the activity of the identified transcriptional enhancer proteins. These studies will aid in the understanding of how T cells infected with this virus escape normal control mechanisms to grow autonomously in the absence of IL2. In addition, these studies will provide further insight to the control mechanisms active in normal T cells important to the study of AIDS and other diseases of the immune system.